For fixed-duration therapies against chronic lymphocytic leukemia (CLL), undetectable measurable residual disease (MRD) predicts overall and progression-free survival more accurately than complete remission. For indefinite therapies, MRD status can direct discontinuation of treatment. We systematically reviewed the relationship between antineoplastic drug exposures and undetectable MRD in CLL. Seventeen trials from MEDLINE and EMBASE met the inclusion criteria; four of which evaluated drug exposures in relation to MRD status. Undetectable MRD was associated with higher trough concentrations of ofatumumab and alemtuzumab, as well as increased maximum concentration and area under the plasma concentration curve (AUC) of ibrutinib. One study found an association between high rituximab AUC and undetectable MRD until adjusting for tumor burden. The limited studies, lack of exposure measurements of concomitant drugs, and high heterogeneity in designs limit the results' generalizability. Further research is needed to explore the exposure-MRD relationship and the possibility for therapeutic drug monitoring in CLL.

SETBP1 mutations (m) have been previously reported in myeloid neoplasms and are associated with poor prognostic co-mutations and cytogenetic abnormalities. We retrospectively analyzed the charts of 113 patients diagnosed with myeloid neoplasms with SETBP1m. The most common diagnosis was MDS (31%). Cytogenetics were abnormal in 51 cases (46.4%), with monosomy 7 being the most common (41.1%). The most frequent co-mutations were ASXL1 (71.7%), SRSF2 (46.9%), TET2 (20.4%). Higher SETBP1m VAF was associated with proliferative features ( < 0.05). Most SETBP1m (96.5%) were in one of three hotspots (Asp868, Gly870, Ile871), with Asp868m being most frequent (51.3%). Patients with Ile871m had higher number of co-mutations (median= 4) compared to Asp868m and Gly870m ( = 0.07). On multivariate analysis, age ≥ 70 years ( = 0.004) and higher peripheral blood blasts ( = 0.02) had worse OS. Patients with Ile871m had lower OS when compared with Asp868m and Gly870m (5.5 months vs. 17.4 and 17 months, respectively,  = 0.1).

ZNF384 gene rearrangements are a distinct subtype of adult B cell acute lymphoblastic leukemia (B-ALL). We screened 46 B-other ALL patients for fusions using fluorescent hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Clinical data, treatment response, and minimal residual disease (MRD) status were analyzed. Ten (21.7%) patients were positive (nine by FISH, nine by RT-PCR, eight by both FISH showed atypical signals, including 3' signal gain and 5' signal deletion. was the main fusion partner ( = 5). TAF15::ZNF384, SYNRG::ZNF384, CREBBP::ZNF384, and TCF3::ZNF384 fusions were found in one patient each; one case's partner gene is unknown. One patient was MRD-negative at the end of the first induction, lower than in patients without r. -r incidence matched B-other ALL incidence in Chinese patients. Combined FISH and RT-PCR improved detection. ALL with -r has unique features, and lower MRD-negative response may indicate a negative impact on traditional treatments.

Multiple myeloma (MM), a malignant plasma cell disorder, remains incurable due to inevitable chemo-resistance development, including carfilzomib (CFZ) leading to relapse and poor patient outcomes. Therefore, new treatment strategies, including using FDA-approved alcohol deterrent disulfiram (DSF) are under investigation. The present study investigated the effect of DSF on ferroptosis and CFZ resistance in MM cells. Our findings indicate that DSF increases the production of cytosolic and mitochondrial reactive oxygen species, and causes a loss of mitochondrial Δψ and an elevation in lipid peroxidation in MM cells. DSF treatment in MM cell lines led to the significant downregulation of ferroptotic genes, including glutathione peroxidase 4. Moreover, ferroptosis inhibitor liproxstatin-1rescued DSF-induced ferroptosis by promoting glutathione peroxidase 4 upregulation. DSF alone overcomes CFZ resistance through lipid peroxidation elevation and acts synergistically with CFZ in CFZ-resistant MM cell lines. Our results suggest that DSF is a promising anti-myeloma agent for overcoming CFZ resistance in MM through ferroptosisinduction.

Allogeneic hematopoietic stem cell transplantation (AHSCT) is currently the only treatment modality that is capable of curing myelofibrosis (MF). Although outcomes of AHSCT have improved vastly in recent years owing to advancements in HLA typing, conditioning regimens, and supportive care, it remains a procedure with a considerable risk in MF patients due to conditioning regimen related toxicity, higher rates of graft failure, infections, and graft versus host disease (GVHD). Recent progress in the treatment and prevention of GVHD with post-transplant cyclophosphamide has also rendered transplantation from alternative donors feasible and safer, thus improving access to patients without HLA-identical donors. Accordingly, all patients with intermediate or high-risk MF today should be referred for potential transplant evaluation to consider the pros and cons of an early versus a delayed transplant strategy. Individual risk assessment in MF is best facilitated by contemporary prognostic models that incorporate both clinical and genetic risk factors. The current review highlights new information regarding risk stratification in MF, anchored by practical algorithms that facilitate patient selection for specific treatment actions, including AHSCT.

Cancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time ( < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning ( = .002), attention ( < .001), language ( < .001), recall ( = .005), and orientation ( < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function ( = 0.68,  < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3  = 0.2,  = .09; for TP3,  = 0.16,  = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP.

New generation therapies such as bispecific antibodies (BsAb), chimeric antigen receptor T-cell therapy (CAR T) and antibody-drug conjugates (ADC) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, there is emerging evidence of increased infection risk associated with these treatments in clinical trials and observational settings. This infection risk may be mediated by on-target, off-tumor side effects such as cytokine release syndrome, hypogammaglobulinaemia and cytopenias, disease-related humoral impairment and the consequences of multiple previous lines of treatment. While bacterial and viral pathogens predominate, reactivation of latent infection and opportunistic infections also warrant attention. This review characterizes the epidemiology of infections associated with novel therapies for RRMM to guide prophylaxis and antimicrobial prescribing in this patient population and highlights future areas of focus to inform ongoing infection prevention strategies.

In the randomized phase III IDHENTIFY trial, the IDH2 inhibitor enasidenib (ENA) showed improvement in event-free but not overall survival compared with conventional care regimens (CCR) among patients with relapsed/refractory (R/R), -mutant AML. We constructed a partitioned survival model to evaluate the cost-effectiveness of enasidenib for the treatment of older patients with R/R, and -mutant AML. In the base-case scenario, ENA exhibited an incremental effectiveness of 0.234quality-adjusted life-years (QALYs) compared to CCR, and an incremental cost of $126,800, leading to an incremental cost-effectiveness ratio of $540,300/QALY(95% CI: $197,800-$4,777,000/QALY). In probabilistic sensitivity analysis, CCR was favored in 99.8% of simulations. The cost of ENA would need to be decreased by 72% to be cost-effective at a willingness-to-pay threshold of $150,000/QALY. Our findings suggest that ENA is unlikely to be a cost-effective treatment for older patients with mutant R/R AML under current pricing.

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies with poor prognosis. AML result from the proliferation of immature myeloid cells blocked at a variable stage of differentiation. Beyond inter-patient heterogeneity, AMLs are characterized by genetic and phenotypic intra-patient heterogeneity. Despite major advances in deciphering AML biology with bulk sequencing studies, pivotal questions remain unanswered. Analyses at the single-cell level could thus transform our understanding of these neoplasms. We review recent progresses in single-cell sequencing technologies from cell processing to bioinformatic pipelines. We next discuss how single-cell applications have helped understand the genetic and functional intra-leukemic heterogeneity, emphasizing aspects related to leukemic stem cells, clonal evolution and measurable residual disease (MRD) monitoring. We finally delineate how single-cell technologies could be implemented in routine clinical practice to improve patient management.

Myelodysplastic syndromes (MDSs) treatment focuses on improving quality of life (QOL), affected by anemia and transfusion dependence (TD). Using the MDS-CAN registry, we studied how changes in transfusion status - TD to transfusion independence (TI) (group A), or vice versa (group B), and maintaining TD (group C) or TI (group D) - affected OS and QOL in 1120 MDS patients. Analysis showed superior OS for those remaining TI, poorer for those remaining TD, and intermediate for those with changes. Among 656 treated patients, group A ( = 54) showed improved QOL, with trends toward improved physical and social function scores. Group B ( = 151) experienced declines in global QOL measures after switching to TD, particularly in fatigue and physical, role, and social functioning. Group C had notable fatigue worsening, while group D showed milder declines across multiple QOL aspects. Achieving TI in MDS correlates with improved QOL, whereas reverting to TD more significantly worsens overall QOL and function scores.

Clinical trials are crucial for improving patient outcomes. Although a significant number of trials are discontinued prematurely, our understanding of factors influencing early termination is limited. We conducted a comprehensive search of ClinicalTrials.gov to identify leukemia trials from 2000 to 2020, followed by data abstraction performed by two independent reviewers. Among 3522 leukemia clinical trials identified, 28.4% were terminated prematurely. Slow accrual was the leading cause of termination 38.2%. The termination rate increased significantly from 17.0% between 2000 and 2005 to 30.9% between 2010 and 2015 ( < .001). Large trials had a lower termination rate than small trials ( < .001). Academic-sponsored trials had the highest termination rates compared to other sponsors' trials ( < .001). Early-phase trials showed higher termination rates compared to late-phase ( < .001). Other significant factors included a sequential assignment, single-center, and non-randomized trials ( < .001). Much of leukemia trials are terminated prematurely, with slow accrual being the most common reason for early termination.

Efforts to produce adoptive cell therapies in AML have been largely unfruitful, despite the success seen in lymphoid malignancies. Identifying targetable antigens on leukemic cells that are absent on normal progenitor cells remains a major obstacle, as is the hostile tumor microenvironment created by AML blasts. In this review, we summarize the challenges in the development of adoptive cell therapies such as CAR-T, CAR-NK, and TCR-T cells in AML, discussing both autologous and allogeneic therapies. We also discuss methods to address myelotoxicity associated with these therapies, including rapidly switchable CAR platforms and CRISPR-Cas9 genetic engineering of hematopoietic stem cells. Finally, we present the current clinical landscape in these areas, along with future directions in the field.

In the absence of head-to-head randomized trials, unanchored matching-adjusted indirect comparisons were conducted to estimate the relative efficacy of zanubrutinib versus ibrutinib and zanubrutinib versus rituximab in relapsed or refractory marginal zone lymphoma (MZL). Logistic propensity score models were used to estimate weights for the patient-level data from two phase II single-arm trials, MAGNOLIA and BGB-3111-AU-003, such that their characteristics matched the ibrutinib and rituximab aggregate-level data from PCYC-1121 and CHRONOS-3, respectively. The base case model for each comparison incorporated four key prognostic factors: prior lines of therapy, MZL subtype, response to prior therapy, and age. A sensitivity analysis incorporating additional prognostic factors was also conducted for the ibrutinib comparison. The impact of each covariate was explored a leave-one-out analysis. Compared with ibrutinib and rituximab, zanubrutinib demonstrated significant benefits in terms of both overall response and progression-free survival in patients with previously treated MZL.

Multiple myeloma is a hematologic malignancy that predominantly affects older individuals, in whom frailty is prevalent. Frailty is a clinical syndrome characterized by decreased reserve and increased vulnerability to stressors, leading to decreased functional capacity. Frailty is prevalent in older individuals and negatively impacts treatment outcomes. In this review, we summarize the tools and strategies used to assess frailty in patients with multiple myeloma, review data describing treatment outcomes in frail adults with multiple myeloma using clinical trial and real-world evidence and evaluate the potential relationship of frailty with quality of life and patient-reported outcomes during therapy for multiple myeloma. Frailty-adapted therapy for MM has the potential to improve treatment outcomes for older adults with myeloma.